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Biomedical subjects

S Shousha

Publications and source records attributed to S Shousha.

At least 55 records · Page 3Linked to original sources

Differential expression of gp200-MR6 molecule in benign hyperplasia and down-regulation in invasive carcinoma of the breast.

In this study, we used immunohistochemical and biochemical analysis to show that gp200-MR6, a 200 kDa molecule that is functionally associated with the human interleukin 4 (IL-4) receptor complex, is expressed at high levels on normal breast epithelial tissues, at lower levels on in situ carcinomas, and that the expression is lost in the invasive carcinoma of the breast. Furthermore, a preliminary study showed that benign epithelial hyperplasia of the breast expresses the gp200-MR6 heterogeneously. Two populations of cells have been observed: MR6 positive and MR6 negative. Interestingly, MR6-positive cells were observed to have different morphology from those that were MR6 negative; the nuclei of the former were larger and rounded in shape, whereas the nuclei of the latter were relatively small and oval in shape. In sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting, monoclonal antibody MR6 detects the same molecular weight molecule in both normal and transformed tissue, indicating that the molecule is not a product of a truncated gene. The intensity of the gp200-MR6 bands correlates with the immunohistochemical data, indicating that the molecule is expressed at high levels in normal tissue and at lower levels in malignant tissue. These results suggest that analysis of gp200-MR6 expression may be useful in tumour grading and prognostic evaluation in breast cancer. Moreover, the molecule may be involved early in the process of tumorigenesis of the breast, in which a loss or a down-regulation of gp200-MR6 could contribute towards tumour development and progression via an effect on cell growth and differentiation.

Antigens, CD↗

Keratin 19 mRNA measurement to detect micrometastases in lymph nodes in breast cancer patients.

We have used polymerase chain reaction (PCR) to measure keratin 19 mRNA in order to detect breast cancer cells invading axillary lymph nodes. In a consecutive series of 125 patients with primary breast cancer, 75 patients had no evidence of lymph node involvement by conventional histology. A total of 530 lymph nodes from these patients were examined and 106 (20%) gave a keratin 19 product detectable by Southern hybridisation. This correlated with primary tumour size (P<0.001). These 106 nodes came from 23 patients. Thus, using this technique, 23/75 (30.6%) patients were found to have evidence of lymph node involvement who would otherwise have been designated lymph node negative.

Adult↗

Immunohistochemical identification of tumours of adipocytic differentiation using an antibody to aP2 protein.

AIM: To determine whether aP2 expression is a useful diagnostic marker in soft tissue tumour pathology. METHODS: A polyclonal antibody to aP2 was used to investigate the immunohistochemical expression of this protein in benign and malignant tumours of adipocytic differentiation and a wide variety of other neoplasms. RESULTS: aP2 was only expressed by lipoblasts (in all types of liposarcoma and in lipoblastomatosis) and by brown fat cells (in both hibernomas and normal periadrenal fetal fat). Other benign adipose tissue tumours and malignant connective tissue or epithelial tumours were distinguished from liposarcoma by the absence of staining for aP2. CONCLUSION: Identification of lipoblasts using markers of aP2 expression is of value in the differential diagnosis of benign and malignant adipose tissue tumours and in distinguishing liposarcomas from other malignant mesenchymal and epithelial neoplasms, some of which contain cells that morphologically resemble lipoblasts.

Adipose Tissue, Brown↗

Keratin 19 in paraffin sections of medullary carcinoma and other benign and malignant breast lesions.

This investigation was aimed at studying the distribution of keratin 19 in various histological types of invasive breast carcinoma and benign breast lesions using two different antibodies, comparing the results, and assessing the significance of the finding. In particular, the usefulness of using the absence of keratin 19 immunostaining as a marker for medullary carcinoma was examined. Paraffin sections of 49 invasive breast carcinomas and 40 benign lesions were examined by the avidin-biotin complex immunoperoxidase technique using two commercially available keratin 19-specific monoclonal antibodies, BA17 and RCK 108. The results showed that the latter antibody stained more cases and the intensity of its staining was more pronounced than BA17. Most medullary and poorly differentiated invasive ductal carcinomas were BA17 negative and RCK108 negative or weakly positive. Moderately and well-differentiated ductal, invasive lobular, tubular, and most mucinous carcinomas were mostly positive with both antibodies, whereas a case of signet ring and a case of spindle cell carcinoma were negative with the two antibodies. Thirty eight of the 40 benign lesions examined showed variable numbers of positive cells, reflecting in general the pattern seen in normal ducts and acini. It is concluded that although keratin 19 seems to be completely absent or at most only weakly represented in paraffin sections of medullary carcinoma, similar reactions are obtained with poorly differentiated ductal tumors. Different antibodies may give different reactions, but well-differentiated ductal and invasive lobular tumors are usually more strongly stained, whereas signet ring and spindle cell carcinomas seem to be negative.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers, Tumor↗

Detection of breast cancer micrometastases in axillary lymph nodes by using polymerase chain reaction.

Breast cancer micrometastases in axillary lymph nodes have been detected by serial sectioning and immunohistochemistry, and shown to have prognostic significance. We have used polymerase chain reaction (PCR) to see whether we could further improve the detection rate of micrometastases. Fifty-seven axillary lymph nodes from patients with breast cancer were examined histologically to assess the proportion of tumor involvement. Immunohistochemical staining with the use of an anti-keratin 19 antibody confirmed the histological findings. Reverse transcription PCR was then performed on extracted RNA by using K19 primers, and all 18 histologically involved nodes yielded the expected 460-base pair product. Of 39 histologically negative nodes, 4 (10%) gave K19 bands detectable with ethidium staining and a further 10 (28%) gave K19 bands after Southern hybridization. To further increase the detection sensitivity a two stage amplification was performed by using nested primers, and K19 product was found in lymph nodes from patients without cancer, as well as in all the nodes from cancer patients. This was shown to be genuine low level expression from endogenous mRNA template, and not derived from amplification of a K19 pseudogene. Reducing the number of PCR cycles in the two amplification steps did not allow sufficient discrimination between normal nodes and those involved nodes in which K19 expression was only detectable after Southern hybridization. The optimal "cut-off" point to distinguish involved nodes from normal nodes remained at the level of 40 cycles of PCR and Southern hybridization. PCR, using K19 as a tumor marker, has been demonstrated in this study to improve the detection of micrometastases in axillary lymph nodes in patients with breast cancer: sensitivity is limited by the specificity of the tumor marker.

Adult↗

Demonstration of oestrogen receptors in paraffin wax sections of breast carcinoma using the monoclonal antibody 1D5 and microwave oven processing.

This study aimed at assessing the usefulness of a new monoclonal antibody (1D5) for the demonstration of oestrogen receptors (ER) in paraffin wax sections, using brief microwave processing rather than proteolytic predigestion. Routinely processed paraffin wax sections of 50 cases of breast carcinoma with known ER concentrations, estimated by the standard dextran-coated charcoal (DCC) biochemical assay, were examined using the avidin-biotin complex-immunoperoxidase technique. The results were assessed semiquantitatively, using a five grade scoring system. Of the 50 cases examined, 37 were positive and six were negative by both DCC and immunohistology. Of the remaining seven cases, three (6%) were negative by DCC but positive with immunohistology, and four (8%) were positive with DCC and negative with immunohistology. The DCC results of the latter four cases were 10, 14, 14 and 16 fmol/mg protein which is at the lowest level of positivity, our cutoff point being less than 10 fmol. The monoclonal antibody 1D5, as used in this study, can provide easily assessed reliable information about the ER status of breast carcinoma using routinely processed paraffin wax sections.

Antibodies, Monoclonal↗

Epstein-Barr virus in gastric carcinoma and adjacent normal gastric and duodenal mucosa.

AIM: To look for Epstein-Barr virus (EBV) in a series of gastric cancers of common and rare histological types. METHODS: Formalin sections from 19 cases of gastric carcinomas of different types were studied using in situ hybridisation with fluorescein conjugated EBER oligonucleotides and the avidin-biotin complex immunoperoxidase technique, using the monoclonal antibody Dako-EBV CS 1-4. RESULTS: The only positive tumour was a lymphoepithelioma-like gastric carcinoma. The remaining 18 cases, which included 11 consecutive cases of usual adenocarcinomas, three early gastric cancers, two adenosquamous carcinomas, and a case each of signet ring carcinoma and neuroepithelioma, were all negative. However, scattered EBV positive cells were seen in the normal gastric or duodenal mucosa bordering the tumours in seven out of 11 cases. CONCLUSIONS: Lymphoepithelioma-like gastric carcinoma seems to be the main, if not the only, EBV positive gastric cancer. The presence of EBV positive normal gastric and duodenal cells suggests that these cells may act as a reservoir for the virus in some people--a possibility that deserves wider investigation.

Adult↗

Prognostic value of nucleolar organizer regions in colorectal neoplasia.

The aims of the study were, firstly, to determine the frequency of nucleolar organizer regions (NORs) in normal colonic mucosa, adenomas and carcinomas, secondly, to determine the relationship of NOR frequency to adenoma diameter, carcinoma stage, patient survival and tumour recurrence. NOR frequency was determined in invasive carcinoma and adjacent normal mucosa in resection specimens from 46 patients with colorectal carcinoma and in 15 colorectal adenomas obtained at colonoscopy. NOR frequency was correlated with conventional prognostic criteria: adenoma diameter and carcinoma stage, tumour recurrence and patient survival. NOR frequency was significantly (P = 0.02) greater in carcinoma (median = 3.64) and adenoma (median = 2.30) compared to non-neoplastic mucosa (median = 1.96). NOR frequency was not significantly related to adenoma diameter, carcinoma node status, patient survival or tumour recurrence. NOR frequency increases with progression through adenoma to carcinoma. The poor association with conventional prognostic factors suggests that NOR frequency is of no value in prediction of adenoma or carcinoma behaviour and therefore does not closely reflect factors determining malignant cell behaviour.

Adenocarcinoma↗

c-erbB-2 oncoprotein in screen-detected breast carcinoma: an immunohistological study.

This study was aimed at comparing screen-detected and symptomatic breast carcinomas with regard to the prevalence of positive immunostaining for c-erb-B-2 oncoprotein. Paraffin sections of 81 breast carcinomas detected through the National Screening Programme were examined for the over-expression of c-erbB-2 oncoprotein using the avidin-biotin immunoperoxidase technique and 2 different specific antibodies: 21N and 4D5. Twenty-one other carcinomas detected in symptomatic patients were similarly examined for comparison. The screen-detected lesions were of 2 types: palpable and impalpable which required needle localization prior to surgical removal. Of the 81 screen-detected tumours, only 8 were c-erbB-2 positive, compared with 5 out of 21 non-screen-detected tumours. When only invasive carcinomas were considered, 5 out of 63 screen-detected cases were positive, compared with 5 out of 15 symptomatic cases. Four out of the 5 screen-detected positive invasive carcinomas were clinically palpable. Our results show an obvious trend towards a lower prevalence of c-erbB-2 oncoprotein over-expression in screen-detected carcinomas. As this over-expression is thought to be associated with increased tumour aggressiveness, the findings suggest a low prevalence of aggressive tumours in screen-detected lesions, particularly impalpable invasive carcinomas, identified so far.

Breast Neoplasms↗

An immunohistochemical study of the long-term effects of androgen administration on female-to-male transsexual breast: a comparison with normal female breast and male breast showing gynaecomastia.

This study was aimed at assessing the effects of therapeutic long-term administration of androgens on normal human female breast. Sections from mastectomy specimens of 29 female-to-male transsexuals who had prolonged androgen administration prior to surgery were examined using routine light microscopy and immunohistochemical techniques. For comparison, sections from ten 'normal' female breast reduction mammoplasty specimens and ten cases of gynaecomastia were similarly examined. Haematoxylin and eosin-stained sections were assessed for the prevalence of elements of the normal breast and benign breast lesions. Immunoperoxidase techniques were performed to study the distribution of a variety of breast-associated antigens and receptors. The results were assessed semi-quantitatively. The prevalence of normal acini and ducts, fibrosis, cysts, and apocrine metaplasia in transsexual specimens was not statistically different from that seen in normal controls. However, transsexual specimens had a significantly higher prevalence of microcalcification than normals. The majority of transsexual specimens were positive for gross cystic disease fluid protein-15, lactoferrin, and progesterone and oestrogen receptors, and negative for B72.3 and pS2. These findings were not significantly different from those in normal controls. All ten gynaecomastia specimens were positive for oestrogen and progesterone receptors. The prevalence of oestrogen receptors was significantly higher than that seen in transsexuals and normal controls, but the prevalence of progesterone receptors was only significantly higher than that seen in transsexuals. It is concluded that long-term androgen administration does not appear to have any significant lasting effect on the normal human female breast, as demonstrated by a wide range of histological and immunohistological criteria.

Adult↗

Immunohistochemical localisation of pS2 protein in ductal carcinoma in situ and benign lesions of the breast.

The expression of pS2 was examined histochemically in paraffin sections taken from biopsy material from patients diagnosed with ductal carcinoma in situ (DCIS). Often intense immunoreactivity, to an anti-pS2 monoclonal antibody, was observed in comedo, solid, cribriform and micropapillary types of DCIS, with significant positivity found in 63-67% of cases. In 15 samples analysed, we found a good correlation between pS2 expression and presence of progesterone receptor positive cells, but not with estrogen receptor. There was only a limited degree of correspondence between the cells staining with these anti-sera. Some pS2 positive cells were also seen in normal acini in areas adjacent to cancer but much less frequently in sections of normal breast from reduction mammoplasty. Most normal areas were negative, as were cysts. In benign proliferative conditions (seen in sections with and without DCIS) such as adenosis, sclerosing adenosis, mild and florid ductal epithelial hyperplasia, significant pS2 positivity was seen in about 50% of cases. These results suggest that there is a progressive increase in pS2 from normal to benign to cancer cells and that this gene is expressed in both the invasive and pre-invasive forms of breast cancer.

Biopsy↗

Helicobacter pylori and intestinal metaplasia: comparison between British and Yemeni patients.

There have been suggestions linking gastric carcinoma with Helicobacter pylori on the one hand and type III intestinal metaplasia on the other hand. This study was aimed at investigating the relationship between intestinal metaplasia and its subtypes, and the presence or absence of H. pylori in gastric biopsies from two geographically different patient populations, one with a much higher prevalence of H. pylori than the other. Antral biopsies from 179 British and 123 Yemeni patients with dyspepsia were examined. Sections stained with hematoxylin and eosin, Alcian blue/periodic acid-Schiff, high iron diamine/Alcian blue, and Warthin-Starry stains were used to assess the presence or absence of inflammation, H. pylori, and intestinal metaplasia with its three subtypes. Although Yemeni patients had a significantly higher prevalence of H. pylori than British patients (113/123. 92% vs. 83/179, 46% respectively; p < 0.001), Yemeni patients had a significantly lower prevalence of all types of intestinal metaplasia (23/123, 19% vs. 60/179, 34%; p < 0.001), as well as type III metaplasia (4/123, 3% vs. 39/179, 22%, p < 0.001). These trends persisted when only patients above the age of 40 yr were considered. However, in British patients, intestinal metaplasia was more commonly seen in those with H. pylori than in those without (36/83, 43%, and 24/96, 25%, respectively, p < 0.01), although the prevalence of type III metaplasia was not significantly different in the two groups (23/83, 28% vs. 16/96, 17%, respectively). The contrasting findings in the two patient populations suggest the presence of other factors, possibly genetic, which control the development of intestinal metaplasia and possibly gastric carcinoma in H. pylori-positive patients.

Adolescent↗

pS2 immunostaining of colorectal carcinoma.

This study was aimed at assessing the significance of pS2 immunostaining in colorectal adenocarcinoma and adjacent tissue. Paraffin sections of 63 surgically resected colorectal adenocarcinomas were stained with a pS2 specific monoclonal antibody using the avidin-biotin complex immunoperoxidase technique. Several tumor sections also included adjacent nonneoplastic mucosa. Six tubular adenomas and five hyperplasic polyps found in the resected bowels were also examined. Focal staining for pS2 was seen in 32 tumors (51%). In all but one case, less than 10% of the tumor cells were stained. pS2 staining was more common in right-sided than in left-sided tumors (p < 0.05), and was more prevalent in Dukes C than combined Dukes A and B tumors (p < 0.05). No significant relationship was found between pS2 positivity and the degree of tumor differentiation, patients' sex, or outcome of the disease as judged by the development of recurrence or metastasis. Strong pS2 positivity was seen in hyperplastic polyps and in nonneoplastic mucosa adjacent to many tumors. Tubular adenomas were either negative or showed focal superficial staining. It is concluded that pS2 immunostaining in colorectal adenocarcinoma does not seem to have prognostic significance, but may reflect developmental differences between the right and left side of the colon. The presence of pS2 staining in adjacent nonneoplastic mucosa and in hyperplastic polyps suggests that the epithelium in these areas is of a regenerative or reactive nature.

Adenocarcinoma↗

An immunohistochemical survey of pS2 expression in human epithelial cancers.

The oestrogen-inducible pS2 protein isolated from human breast-cancer cells appears to have prognostic significance in breast-cancer patients. Using both monoclonal and polyclonal pS2 anti-sera, we have carried out an immunocytochemical survey of 9 epithelial cancers. Some degree of specific tumour staining was observed in 4 tissues, the extent varying greatly between specimens. Most (11/13) of the colorectal cancers showed immunoreactivity, as did 4/5 pancreatic carcinomas. In some of these cases, patchy staining was also observed in adjacent non-tumour cells. Two bronchio-alveolar carcinomas showed positivity, but 5 poorly differentiated adenocarcinomas of the lung did not. In the ovary, staining was observed in 3/3 mucinous cystadenocarcinomas but only in 1/8 of the serous type. No reactivity was seen in specimens of salivary gland, kidney, liver, prostate or uterus. This pilot study indicates that pS2 may be a useful marker of adenocarcinomas in human neoplasms apart from those in the breast, and suggests that more extensive surveys might be worthwhile.

Adenocarcinoma↗